REAL

Macrophage inflammatory and regenerative response periodicity is programmed by cell cycle and chromatin state

Daniel, Bence and Belk, Julia A. and Meier, Stefanie L. and Chen, Andy Y. and Sandor, Katalin and Czimmerer, Zsolt and Varga, Zsófia and Bene, Krisztián and Buquicchio, Frank A. and Qi, Yanyan and Kitano, Hugo and Wheeler, Joshua R. and Foster, Deshka S. and Januszyk, Michael and Longaker, Michael T. and Chang, Howard Y. and Satpathy, Ansuman T. (2023) Macrophage inflammatory and regenerative response periodicity is programmed by cell cycle and chromatin state. MOLECULAR CELL, 83 (1). 121-138.e7. ISSN 1097-2765

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Abstract

Cell cycle (CC) facilitates cell division via robust, cyclical gene expression. Protective immunity requires the expansion of pathogen-responsive cell types, but whether CC confers unique gene expression programs that direct the subsequent immunological response remains unclear. Here, we demonstrate that single macrophages (MFs) adopt different plasticity states in CC, which leads to heterogeneous cytokine-induced polarization, priming, and repolarization programs. Specifically, MF plasticity to interferon gamma (IFNG) is substantially reduced during S-G2/M, whereas interleukin 4 (IL-4) induces S-G2/M-biased gene expression, mediated by CC-biased enhancers. Additionally, IL-4 polarization shifts the CC-phase distribution of MFs toward the G2/M phase, providing a subpopulation-specific mechanism for IL-4-induced, dampened IFNG responsiveness. Finally, we demonstrate CC-dependent MF responses in murine and human disease settings in vivo, including Th2-driven airway inflammation and pulmonary fibrosis, where MFs express an S-G2/M-biased tissue remodeling gene program. Therefore, MF inflammatory and regenerative responses are gated by CC in a cyclical, phase-dependent manner. © 2022 Elsevier Inc.

Item Type: Article
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 25 Sep 2023 10:50
Last Modified: 25 Sep 2023 10:50
URI: http://real.mtak.hu/id/eprint/174771

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